The objective of the current application is to investigate novel formulations for mucosal immunization against HIV. An important goal for an effective vaccination strategy against HIV should be the induction of local mucosal immunity to provide a first line defense against pathogen infection, in addition to the traditional systemic immunity. Vaccines that protect against infection with HIV are predicted to not only have an effect on disease but also on the epidemiological parameters of virus spread across populations. The specific aims of the current application consist in generating novel biocompatible microparticles (PulmoSpheres TM) loaded with gp120 antigen for the development of mucosal vaccines against HIV. Variants engineered with immune modulatory excipients like mannose-receptor binding carbohydrates dendritic cell chemokines, Th1-promoting or IgA-inducing cytokines will be designed and compared regarding the biological activity. This will entail systematic evaluation of different formulations with the aim of engineering the particle to provide a maximal immune response. Efficacy testing will be carried out in well-defined animal models using an accepted array of immunologic assays aimed to characterize the specific B and T cell responses to vaccination, both quantitatively and qualitatively.